Registration Methodology for Histological Sections and In Vivo Imaging of Human Prostate

Rationale and Objectives

Registration enables quantitative spatial correlation of features from different imaging modalities. Our objective is to register in vivo imaging with histologic sections of the human prostate so that histologic truth can be correlated with in vivo imaging features.

Materials and Methods

In vivo imaging of the prostate included T2-weighted anatomic and diffusion weighted 3-T magnetic resonance imaging (MRI) as well as 11 C-choline positron emission tomography (PET). In addition, ex vivo 3-T MRI of the prostate specimen, histology, and associated block face photos of the prostate specimen were obtained. A standard registration method based on mutual information (MI) and thin-plate spline (TPS) was applied. Registration among in vivo imaging modalities is well established; however, accurate registration involving histology is difficult. Our approach breaks up the difficult direct registration of histology and in vivo imaging into achievable subregistration tasks involving intermediate ex vivo modalities like block face photography and specimen MRI. Results of subregistration tasks are combined to compute the intended, final registration between in vivo imaging and histology.

Results

The methodology was applied to two patients and found to be clinically feasible. Overall registered anatomic MRI, diffusion MRI, and 11 C-choline PET aligned well with histology qualitatively for both patients. There is no ground truth of registration accuracy as the scans are real patient scans. An indirect validation of the registration accuracy has been proposed comparing tumor boundary markings found in diffusion MRI and histologic sections. Registration errors for two patients between diffusion MRI and histology were 3.74 and 2.26 mm.

Conclusion

This proof of concept paper demonstrates a method based on intrinsic image information content for successfully registering in vivo imaging of the human prostate with its post-resection histology, which does not require the use of extrinsic fiducial markers. The methodology successfully mapped histology onto the in vivo imaging space, allowing the observation of how well different in vivo imaging features correspond to histologic truth. The methodology is therefore the basis for a systematic comparison of in vivo imaging for staging of human prostate cancer.

Registration is a process that establishes a spatial correspondence between two scans so that both can be viewed in the same spatial frame. Often registration is a necessary preprocessing step before a quantitative comparison can be made between two scans, as it is difficult to locate exactly corresponding spatial features in both scans free of personal bias. Here we present a method to register histology sections with various in vivo images, including anatomical magnetic resonance imaging (MRI), diffusion MRI, and positron emission tomography (PET), of human prostate. Histology slides carry the “ground truth” regarding location and extent of tumors determined by a pathologist. Once mapped onto the in vivo imaging space, we can observe how different features of in vivo imaging help to characterize tumor and normal tissues determined by histology. We can observe how well anatomical MRI, diffusion MRI, and PET differentiate between normal and tumor tissues for prostate cancer. This information will enable us to determine which modality or combination of modalities is suited best to stage prostate cancer. The current practice of staging prostate cancer uses anatomical MRI and/or transrectal ultrasound (TRUS), both of which have unsatisfactory accuracy ( ).

Registration of histology sections and in vivo imaging modalities is a challenging problem. The key issue is to account for the complex deformations that occur in the prostate as it is removed from the body and then sectioned for histological evaluation. First, the prostate potentially undergoes nonlinear deformation as it is removed from the body, because there are no surrounding organs to constrain the prostate and vascular pressurization and intracellular fluids are lost. Second, the prostate is further deformed as it is fixed and then sliced for histological evaluation. The other challenge is the difference in available information between in vivo imaging (e.g., resolution in millimeters) and histology (e.g., resolution in microns). Registration among in vivo imaging modalities is relatively easy, as the deformation involved is less drastic than deformation involved with registering histology.

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Materials and methods

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Registration Framework

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Scan Acquisition

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Registration Schematic

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Results

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Registration Results: Patient 1

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Registration Results: Patient 2

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Intermediate Registration Between Stacked Block Photographs and Ex Vivo MRI

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Registration Error from Two Patients

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Discussion

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Conclusion

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References

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Registration Methodology for Histological Sections and In Vivo Imaging of Human Prostate

Rationale and Objectives

Materials and Methods

Results

Conclusion

Materials and methods

Registration Framework

Scan Acquisition

Registration Schematic

Results

Registration Results: Patient 1

Registration Results: Patient 2

Intermediate Registration Between Stacked Block Photographs and Ex Vivo MRI

Registration Error from Two Patients

Discussion

Conclusion

References

Further Reading

Abstracts of Funded National Institutes of Health Grants

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